title: Interaction between very-KIND Ras guanine exchange factor and microtubule-associated protein 2, and its role in dendrite growth--structure and function of the second kinase noncatalytic C-lobe domain.
abstract: The kinase noncatalytic C-lobe domain (KIND) is a putative protein-protein interaction module. Four KIND-containing proteins, Spir-2 (actin-nuclear factor), PTPN13 (protein tyrosine phosphatase), FRMPD2 (scaffold protein) and very-KIND (v-KIND) (brain-specific Ras guanine nucleotide exchange factor), have been identified to date. Uniquely, v-KIND has two KINDs (i.e. KIND1 and KIND2), whereas the other three proteins have only one. The functional role of KIND, however, remains unclear. We previously demonstrated that v-KIND interacts with the high-molecular weight microtubule-associated protein 2 (MAP2), a dendritic microtubule-associated protein, leading to negative regulation of neuronal dendrite growth. In the present study, we analyzed the structure-function relationships of the v-KIND-MAP2 interaction by generating a series of mutant constructs. The interaction with endogenous MAP2 in mouse cerebellar granule cells was specific to v-KIND KIND2, but not KIND1, and was not observed for the KINDs from other KIND-containing proteins. The binding core modules critical for the v-KIND-MAP2 interaction were defined within 32 residues of the mouse v-KIND KIND2 and 43 residues of the mouse MAP2 central domain. Three Leu residues at amino acid positions 461, 474 and 477 in the MAP2-binding core module of KIND2 contributed to the interaction. The MAP2-binding core module itself promoted dendrite branching as a dominant-negative regulator of v-KIND in hippocampal neurons. The results reported in the present study demonstrate the structural and functional determinant underlying the v-KIND-MAP2 interaction that controls dendrite arborization patterns.
authors.affiliation: Laboratory for Molecular Neurogenesis, RIKEN Brain Science Institute, Saitama, Japan.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Huang
authors.forename: Asako
authors.initials: A
authors.lastname: Furuya
authors.forename: Kanehiro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Teiichi
authors.initials: T
authors.lastname: Furuichi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D003712:Dendrites / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D007930:Leucine / Q000737:chemistry; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13 / Q000378:metabolism; D020663:ras Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D020663:ras Guanine Nucleotide Exchange Factors; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; C516743:Ptpn13 protein, mouse; D007930:Leucine